Immortalized Human Hepatic Cell Lines for In Vitro Testing and Research Purposes

Ramboer, Eva; Vanhaecke, Tamara; Rogiers, Vera; Vinken, Mathieu

doi:10.1007/978-1-4939-2074-7_4

Cited by 51 publications

(46 citation statements)

References 137 publications

(146 reference statements)

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“…The identification and ectopic expression of viral oncogenes made it possible to "immortalize" post-mitotic cells resulting in their cell cycle reentry and subsequent proliferation (185). Especially the simian virus 40 large T antigen (SV40 Tag), due to its ability to suppress the activity of pRb and p53, has been extensively used to generate lines of permanently immortalized parenchymal mammalian cells (e.g., hepatocytes, neurons, skeletal muscle cells and so forth) that could be used as platform for drug screenings and disease modeling (185)(186)(187)(188).…”

Section: Immortalized Amsmentioning

confidence: 99%

Multicellular In vitro Models of Cardiac Arrhythmias: Focus on Atrial Fibrillation

Gorp

Trines

Pijnappels

et al. 2020

Front. Cardiovasc. Med.

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Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice with a large socioeconomic impact due to its associated morbidity, mortality, reduction in quality of life and health care costs. Currently, antiarrhythmic drug therapy is the first line of treatment for most symptomatic AF patients, despite its limited efficacy, the risk of inducing potentially life-threating ventricular tachyarrhythmias as well as other side effects. Alternative, in-hospital treatment modalities consisting of electrical cardioversion and invasive catheter ablation improve patients' symptoms, but often have to be repeated and are still associated with serious complications and only suitable for specific subgroups of AF patients. The development and progression of AF generally results from the interplay of multiple disease pathways and is accompanied by structural and functional (e.g., electrical) tissue remodeling. Rational development of novel treatment modalities for AF, with its many different etiologies, requires a comprehensive insight into the complex pathophysiological mechanisms. Monolayers of atrial cells represent a simplified surrogate of atrial tissue well-suited to investigate atrial arrhythmia mechanisms, since they can easily be used in a standardized, systematic and controllable manner to study the role of specific pathways and processes in the genesis, perpetuation and termination of atrial arrhythmias. In this review, we provide an overview of the currently available two-and three-dimensional multicellular in vitro systems for investigating the initiation, maintenance and termination of atrial arrhythmias and AF. This encompasses cultures of primary (animal-derived) atrial cardiomyocytes (CMs), pluripotent stem cell-derived atrial-like CMs and (conditionally) immortalized atrial CMs. The strengths and weaknesses of each of these model systems for studying atrial arrhythmias will be discussed as well as their implications for future studies.

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Section: Immortalized Amsmentioning

confidence: 99%

Multicellular In vitro Models of Cardiac Arrhythmias: Focus on Atrial Fibrillation

Gorp

Trines

Pijnappels

et al. 2020

Front. Cardiovasc. Med.

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“…Due to most immortalized human hepatic cell lines having reduced liverspecific functionality (52), different strategies have been used to counteract this issue, including co-culture systems with primary human hepatocytes and overexpressing liver-enriched transcription factors, CYP450 enzymes, or proliferation inhibitors to increase hepatic functions (52). Immortalized human hepatic cell lines have been successfully used to investigate the life cycle of hepatitis C and B viruses (53)(54)(55)(56), and they act as cellular models of hepatocarcinogenesis (57) and steatosis (58).…”

Section: Immortalized or Transformed Cell Linesmentioning

confidence: 99%

In Vitro Models of the Liver: Disease Modeling, Drug Discovery and Clinical Applications

Collins

Yuen

et al. 2019

Hepatocellular Carcinoma

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In vitro models of the liver have led to important insights into the pathogenesis of liver disease. These models are essential tools in the discovery and preclinical stages of drug development. The clinical application of these models is also emerging as a promising avenue for validating genetic target-matched treatments, in a precision medicine approach to treatment. Recent advances in 'liver-on-a-chip' technology and liver organoid research have opened up new opportunities for the functional and clinical use of organotypic in vitro models. This chapter focuses on the currently available in vitro liver models and the opportunities and limitations they present in the context of evaluating their use in disease modeling, drug discovery, and clinical application.

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“…It has been demonstrated that with the lack of appropriate levels of CYP expression when compared to PHH, HepG2 cells do not fully represent the phenotype of the in vivo hepatocytes and therefore that the detection of many hepatotoxic compounds utilising the HepG2 cells line is inaccurate, and for non-liver specific toxins this model is ineffectual [63]. It is however still the case that 2D cultures of hepatic-derived cell lines are valuable in the early stages of safety assessments [22] and liver cell lines can still provide a convenient and pragmatic initial tool for early screening and drug safety assessment [64].…”

Section: Hepatic-derived Cell Linesmentioning

confidence: 99%

Impact of cell types and culture methods on the functionality of in vitro liver systems – A review of cell systems for hepatotoxicity assessment

Kyffin

Sharma

Leedale

et al. 2018

Toxicology in Vitro

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Xenobiotic safety assessment is an area that impacts a multitude of different industry sectors such as medicinal drugs, agrochemicals, industrial chemicals, cosmetics and environmental contaminants. As such there are a number of well-developed in vitro, in vivo and in silico approaches to evaluate their properties and potential impact on the environment and to humans. Additionally, there is the continual investment in multidisciplinary scientists to explore non-animal surrogate technologies to predict specific toxicological outcomes and to improve our understanding of the biological processes regarding the toxic potential of xenobiotics. Here we provide a concise, critical evaluation of a number of in vitro systems utilised to assess the hepatotoxic potential of xenobiotics.

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Immortalized Human Hepatic Cell Lines for In Vitro Testing and Research Purposes

Cited by 51 publications

References 137 publications

Multicellular In vitro Models of Cardiac Arrhythmias: Focus on Atrial Fibrillation

Multicellular In vitro Models of Cardiac Arrhythmias: Focus on Atrial Fibrillation

In Vitro Models of the Liver: Disease Modeling, Drug Discovery and Clinical Applications

Impact of cell types and culture methods on the functionality of in vitro liver systems – A review of cell systems for hepatotoxicity assessment

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